This application seeks five years of support to conduct the first population-based twin study of autism spectrum disorder (ASD) with cases ascertained using current day diagnostic criteria. Inferences about the degree of genetic influence on autism depend crucially on the differential concordance of monozygotic (MZ) vs. dizygotic (DZ) cotwins. The results of twin studies affect the plausibility of various linkage approaches. Changing diagnostic practices lead to differences in base rates and in twin proband identification and thus require new studies. In addition, population-based studies of twins are needed to investigate claims that twins are over-represented among ASD cases. Building on extensive data that establish the project's feasibility, we shall collect a sample of virtually all twins aged 2-16 years in the state of Wisconsin, first by screening and case-finding, then by performing full diagnostic and behavioral assessments. We project a final sample of >120 pairs of twins, one or both with ASD; about 80% of the cases should be idiopathic. Given the goal to quantify genetic contributions to ASD, we will also assess the Broader Autism Phenotype in family members. We will characterize co occurring but non-diagnostic behavioral problems (anxiety, motor dyspraxia, sensory sensitivities, sleep problems, and aggressive or self-injurious behavior) as well as other medical conditions. Family functioning will be assessed in the interest of understanding the effects of ASD, and responses to treatment will be monitored in the interest of future translational research. A longitudinal follow-up will allow confirmation of early diagnoses and a measure of the course of ASD. A neuroimaging study, including eye tracking and electrodermal measures, will be conducted on the subsample of twins over 8 years of age, with particular attention paid to the discordant MZ pairs.